Teede et al.

BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

Open Access

REVIEW

Polycystic ovary syndrome: a complex condition

with psychological, reproductive and metabolic
manifestations that impacts on health across the
lifespan
Review

H Teede1,2, A Deeks1 and L Moran*1

Abstract
Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one
in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility,
hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus,
adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of
life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and
involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental
factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity
prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS.
Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased
risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term
reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of
obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at
normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial
initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve
many of the features of PCOS. Management should focus on support, education, addressing psychological factors and
strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of
long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based
guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this
common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses
primarily on the less appreciated cardiometabolic and psychological features of PCOS.
Introduction
Polycystic ovary syndrome (PCOS) is a frustrating experience for women, often complex for managing clinicians
and is a scientific challenge for researchers. As research
in PCOS is rapidly advancing, it is vital that research evidence is translated to knowledge and action among
women, healthcare professionals and policy makers.
PCOS is the most common endocrine abnormality in
* Correspondence: lisa.moran@monash.edu
1

Jean Hailes Clinical Research Unit, School of Public Health and Preventive
Medicine, Monash University, Clayton, Australia
Full list of author information is available at the end of the article

reproductive-age women. The prevalence of PCOS is traditionally estimated at 4% to 8% from studies performed
in Greece, Spain and the USA [1-4]. The prevalence of
PCOS has increased with the use of different diagnostic
criteria and has recently been shown to be 18% (17.8
2.8%) in the first community-based prevalence study
based on current Rotterdam diagnostic criteria [5].
Importantly, 70% of women in this recent study were
undiagnosed [5]. While the upper limit of prevalence for
this study was imputed using estimates of polycystic ovaries (PCO) for women who had not had an ultrasound,
non-imputed prevalences were calculated as 11.9 2.4%

2010 Teede et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

[5]. PCOS has also been noted to affect 28% of unselected

obese and 5% of lean women [5-8]. In 2006, based on US
data and traditionally lower prevalence estimates the
anticipated economic burden of PCOS in Australia was
AU$400 million (menstrual dysfunction 31%, infertility
12% and PCOS-associated diabetes 40% of total costs),
representing a major health and economic burden [8].
With regards to fertility, the estimated cost per birth in
overweight Australian women with PCOS is high [9].
Promisingly, lifestyle intervention comprising dietary,
exercise and behavioural therapy improves fertility and
reduces costs per birth significantly [9].
Aetiology: insulin resistance and hyperandrogenism

The exact pathophysiology of PCOS is complex and

remains largely unclear. Although a detailed discussion is
beyond the scope of this review, the underlying hormonal
imbalance created by a combination of increased androgens and/or insulin underpin PCOS (Figure 1). Genetic
and environmental contributors to hormonal disturbances combine with other factors, including obesity,
ovarian dysfunction and hypothalamic pituitary abnormalities to contribute to the aetiology of PCOS [10,11].
However, greater understanding of pathophysiological
contributors in PCOS have been hampered by a lack of
ideal methods to assess either hyperandrogenism or insulin resistance. Hyperandrogenism is a well established
contributor to PCOS aetiology, detected in around 60% to
80% of cases. Insulin resistance is a pathophysiological
contributor in around 50% to 80% of women with PCOS
[12], especially in those with more severe PCOS diagnosed on National Institutes of Health (NIH) criteria and
in women who are overweight. Conversely, lean women

Figure 1 Schema of aetiology and clinical features including reproductive, metabolic and psychosocial features of polycystic
ovary syndrome (PCOS). Reproduced with permission from [82].

Page 2 of 10

[13] and women with milder PCOS diagnosed on newer

European Society for Human Reproduction (ESHRE)/
American Society of Reproductive Medicine (ASRM) criteria [14] appear to have less severe hyperinsulinaemia
and insulin resistance. , Insulin resistance contributes to
metabolic features but also to reproductive features [15]
through augmenting androgen production and increasing
free androgens by reducing sex hormone binding globulin (SHBG). In this setting of unclear aetiology and mechanisms of insulin resistance, further research is clearly
needed.
Impact of obesity on polycystic ovary syndrome

Obesity and excess weight are major chronic diseases in

Western world countries. Obesity increases hyperandrogenism, hirsutism, infertility and pregnancy complications both independently and by exacerbating PCOS
[16,17]. In general populations, obesity and insulin resistance further increase type 2 diabetes (DM2) and cardiovascular disease (CVD). Likewise, in PCOS obesity
worsens insulin resistance and exacerbates reproductive
and metabolic features [16,17]. Furthermore, women
with PCOS have increased risk factors for DM2 and
CVD, increased impaired glucose tolerance (IGT), DM2
and potentially increased CVD [18]. As obesity rates rise,
the public health significance of PCOS will increase [18].
Treatment of obesity through lifestyle intervention is a
key treatment strategy in PCOS and improves insulin
resistance, reproductive and metabolic features [19].
Diagnosis of PCOS

Until recently no universally accepted clinical definition

existed for PCOS. Over the past three decades, research
has highlighted that PCOS is a heterogeneous condition.
Symptoms and signs related to PCOS have been evaluated and the initial NIH diagnostic criteria based on oligomenorrhoea/amenorrhoea and clinical or biochemical
hyperandrogenism have been broadened in the 2003 Rotterdam or ESHRE/ASRM criteria to include PCO at
ultrasound in the key diagnostic criteria [20]. A total of
25% of young women have PCO on ultrasound and the
inclusion of PCO in diagnostic criteria has increased the
prevalence of PCOS. Recent data indicates that the prevalence of PCOS may be doubled on use of the ESHRE/
ASRM criteria with a prevalence of 12% (not imputing
presence of polycystic ovaries) to 18% (imputing presence
of polycystic ovaries) reported in a community sample
[5]. In 2006 the Androgen Excess PCOS Society suggested further modification of the diagnostic criteria to
exclude those without symptoms (PCO on ultrasound
and oligomenorrhoea/amenorrhoea but no hyperandrogenism) (Table 1) [21]. It should be noted that PCOS is a
diagnosis of exclusion and conditions including thyroid

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

Page 3 of 10

Table 1: The different diagnostic criteria for polycystic ovary syndrome (PCOS)
National Institutes of Health criteria
consensus statement [83]

European Society for Human Reproduction

and Embryology/American Society for
Reproductive Medicine consensus
statement [20]

Androgen Excess Society position

statement [21]

Oligo-ovulation and clinical and/or

biochemical signs of hyperandrogenism, and
exclusion of other aetiologies*

Two out of three of: oligo-ovulation and/or

anovulation, clinical and/or biochemical signs
of hyperandrogenism, or polycystic ovaries,
and exclusion of other aetiologies*

Hyperandrogenism (hirsutism and/or

hyperandrogeniaemia), ovarian dysfunction
(oligoanovulation and/or polycystic ovaries),
and exclusion of other androgen excess
related disorders*

Table adapted from [14], with permission of Oxford University Press, Oxford, UK.
*Congenital adrenal hyperplasia, androgen-secreting tumours, Cushing's syndrome, 21-hydroxylase-deficient non-classic adrenal hyperplasia,
androgenic/anabolic drug use or abuse, syndromes of severe insulin resistance, thyroid dysfunction, hyperprolactinaemia.

dysfunction and hyperprolactinaemia should be excluded

biochemically, whilst more rare conditions should be
excluded clinically (Cushing's syndrome, virilising
tumours, and so on). However, cardiometabolic features
and insulin resistance are not currently part of the PCOS
diagnostic criteria. This is in part attributable to the lack
of accurate methods to measure insulin resistance with
measurement not currently recommended in clinical
practice [22].
With the four key diagnostic features, (oligomenorrhoea/amenorrhoea, clinical or biochemical hyperandrogenism and PCO on ultrasound) there are many potential
phenotypes (Table 1) [21]. This heterogeneity of the condition is further exacerbated by degree of obesity, insulin
resistance, ethnicity and other factors [21]. Both the heterogeneity of PCOS and the lack of an understanding of
its aetiology contribute to the evolving diagnostic criteria
and ongoing controversy. Currently the ESHRE/ASRM or
Rotterdam criteria are the agreed international diagnostic
criteria for PCOS, although further research is needed.
Clinical features of PCOS

Women with PCOS may therefore present with a variety

of serious clinical sequalae including psychological problems (reduced quality of life, poor self-esteem, depression, anxiety) [23,24], reproductive manifestations
(hirsutism, infertility and pregnancy complications) [25],
and metabolic implications (insulin resistance, metabolic
syndrome, IGT, DM2 and potentially CVD) [14,26,27]
(Figure 1 and Appendix 1). Given the heterogeneous
nature of PCOS (Table 1) and the spectrum of clinical
features, presentation can vary across the life cycle. PCOS
is a chronic condition with psychological and reproductive manifestations usually beginning in adolescence then
transitioning to include infertility and increasing metabolic complications over time. However, when combined
with obesity, metabolic implications of PCOS such as
IGT, DM2 and the metabolic syndrome can present in
adolescence [28,29].

Reproductive features of PCOS

Ovarian dysfunction and infertility

Ovarian dysfunction usually manifests as oligomenorrhoea/amenorrhoea resulting from chronic oligo-ovulation/anovulation [30]. However, prolonged anovulation
can lead to dysfunctional uterine bleeding which may
mimic more regular menstrual cycles. The majority of
PCOS patients have ovarian dysfunction, with 70% to
80% of women with PCOS presenting with oligomenorrhoea or amenorrhoea. Among those with oligomenorrhoea, 80% to 90% will be diagnosed with PCOS [30].
Among those with amenorrhoea, only 40% will be diagnosed with PCOS as hypothalamic dysfunction is a more
common cause [31]. Oligomenorrhoea occurs usually in
adolescence, with onset later in life often associated with
weight gain. Menstrual irregularity is then often masked
by the oral contraceptive pill (OCP), until cessation, when
the underlying irregular cycles recur. Menorrhagia can
occur with unopposed oestrogen and endometrial hyperplasia, further exacerbated by elevated oestrogen levels in
obesity. Whilst inadequate research exists, it is generally
recommended that greater than four cycles per year may
protect the endometrium. Women with regular menstrual cycles can also now be diagnosed with PCOS based
on newer diagnostic criteria (Table 1) [21].
PCOS is the most common cause of anovulatory infertility. It accounts for 90% to 95% of women attending
infertility clinics with anovulation. However 60% of
women with PCOS are fertile (defined as the ability to
conceive within 12 months), although time to conceive is
often increased [30]. In those with PCOS and infertility,
90% are overweight. Obesity independently exacerbates
infertility, reduces efficacy of infertility treatment and
induces a greater risk of miscarriage [30]. There is currently an active debate about the appropriate limit for
body mass index for assisted reproduction therapies,
given the reduced success rates and the demonstrated
risks of pregnancy in overweight women [32]. Ideally,
weight should be optimised prior to pregnancy. Age-

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

related infertility also exacerbates infertility and timely

planning of families may warrant discussion.
Hyperandrogenism

The clinical and/or biochemical signs of androgen excess

in PCOS result from increased synthesis and release of
ovarian androgens. Elevated luteinising hormone and
insulin synergistically increase androgen production.
Insulin resistance leads to hyperinsulinaemia, reduces
SHBG and raises free circulating testosterone and
together, hyperandrogenism and hyperinsulinaemia
impairs ovarian follicle development. Clinical hyperandrogenism primarily includes hirsutism, acne and male
pattern alopecia [21]. Hirsutism is defined in females as
male type terminal hair growth and distribution [33].
PCOS is a common cause of hirsutism occurring in
approximately 60% of cases, however this varies with race
and degree of obesity [21]. Hirsutism should be assessed
with a standardised scoring system (Ferriman-Gallwey
score). Acne affects one third of cases and is not particularly specific for PCOS [33]. Male pattern hair loss
(androgenic alopecia) is less frequently seen in PCOS
cases, as it generally requires a familial predisposition.
Other features of hyperandrogenism include virilisation,
which, especially if presenting with clitoromegaly and
rapid onset, requires exclusion of other causes including
adrenal or ovarian androgen-secreting tumours.
Biochemical hyperandrogenism is present in most
patients with PCOS. Measurement of biochemical androgens in PCOS is limited by poor accuracy and reproducibility of assays, which are designed for significantly
higher male androgen levels. Free androgen index measurements are generally recommended, derived in the lab
from SHBG and total testosterone measurements [33].
Dehydroepiandrosterone sulfate (DHEAS) and androstenedione are not routinely recommended in PCOS [21].

Metabolic features of PCOS

Dyslipidaemia

Dyslipidaemia is common in PCOS compared to weight

matched controls [34-37], with higher triglycerides and
lower high density lipoprotein cholesterol [35]. The dyslipidaemia occurs independent of body mass index (BMI)
[35,38] , however there is a synergistic deleterious effect
of obesity and insulin resistance in PCOS analogous to
that seen in DM2. The causes of dyslipidaemia in PCOS
are again multifactorial. Insulin resistance appears to
have a pivotal role mediated in part by stimulation of
lipolysis and altered expression of lipoprotein lipase and
hepatic lipase [35].
Insulin resistance and abnormal glucose metabolism

Insulin resistance occurs in around 50% to 80% of women

with PCOS [12], primarily in the more severe NIH diag-

Page 4 of 10

nosed PCOS and in those who are overweight. Lean

women [13] and milder Rotterdam diagnosed PCOS [14]
appear to have less severe insulin resistance. A full discussion of the complex mechanisms involved in insulin
resistance, hyperinsulinaemia, DM2 and CVD is beyond
the scope of this review. Mechanisms involved in insulin
resistance are likely to be complex with genetic and environmental contributors. Specific abnormalities of insulin
metabolism identified in PCOS include reductions in
secretion [39,40], reduced hepatic extraction [40],
impaired suppression of hepatic gluconeogenesis [41]
and abnormalities in insulin receptor signalling [42].
Interestingly, there is a paradoxical expression of insulin
resistance in PCOS whereby insulin-stimulated androgen
production persists while its role in glucose metabolism
is impaired [42]. Therefore, insulin resistance in PCOS
results in hyperinsulinaemia with its associated diverse
and complex effects on regulating lipid metabolism, protein synthesis and modulation of androgen production.
The cause of insulin resistance is likewise complex and
multifactorial with genetic and environmental contributors [15]. Lean women with PCOS often but not always
[13] have abnormalities of insulin secretion and action
compared to weight-matched control subjects [41].
Where a woman with PCOS is overweight, she may also
demonstrate extrinsic insulin resistance associated with
adiposity, which is potentially mechanistically distinct
from the insulin resistance present in lean women with
PCOS. In women with insulin resistance and PCOS, only
a subgroup develop coexistent pancreatic insufficiency
with cell failure and go on to DM2. In this setting, insulin output cannot overcome resistance and hyperglycaemia develops. Women with PCOS are at increased risk of
developing IGT and DM2 with prevalence rates of 31.3%
and 7.5%, respectively, compared to 14% for IGT and 0%
for DM2 in age-matched and weight-matched non-PCOS
control women [27].
Women with PCOS also develop abnormal glucose
metabolism at a younger age and may demonstrate a
more rapid conversion from IGT to DM2 [43]. The rate of
conversion from IGT to DM2 in a general Australian
population was estimated in the large cohort Australian
Diabetes, Obesity and Lifestyle (AusDiab) study at 2.9%
per year for young females [44]. Another Australian study
has reported a substantially higher conversion rate (8.7%
per year over 6.2 years) in women with PCOS [45], however this has not been uniformly reported [46]. Women
with PCOS also have higher gestational diabetes (GDM)
risk, with a recent meta-analysis reporting an odds ratio
(OR) of 2.94 [25]. The risk of GDM occurs both independent of and is exacerbated by obesity [27,47]. Whilst there
are few adequately powered studies assessing natural history of IGT, DM2 and CVD in PCOS and there is a need
for further research, the International Diabetes Federa-

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

tion has identified PCOS as a significant non-modifiable

risk factor associated with DM2 [48].
It is increasingly clear that IGT is also a clinically relevant state where early identification and intervention
improve long-term outcomes [49]. IGT has been found to
increase the risk of CVD, mortality and progression to
DM2 in general populations [44]. Recent populationbased data noted a mortality rate of 5.5% over 5 years for
those with IGT versus 1.9% with normal glucose tolerance [44]. Furthermore, lifestyle intervention, metformin
and glitazones can prevent IGT progression to DM2 [49],
strengthening the argument for early detection of IGT,
including in high-risk PCOS women
There are currently no generic guidelines for IGT
screening, only for DM2 based on fasting glucose or more
recently on HbA1c as a first line. However, impaired fasting glucose is a poor predictor of IGT in women in general [50] and in PCOS [27,43]. Hence the ESHRE/ASRMsponsored PCOS Consensus Workshop Group recommend an oral glucose tolerance test in all overweight
women with PCOS [51]. Furthermore, emerging data
shows increased risk of metabolic complications in firstdegree family members of women with PCOS [52-56].
Screening for metabolic conditions may be also warranted in relatives of women with PCOS, although this
requires further research.
Cardiovascular disease risk

Alongside insulin resistance, metabolic syndrome, IGT

and DM2, women with PCOS also have increased novel
cardiovascular risk factors (inflammation, oxidative stress
and impaired fibrinolysis) [14]. Also, increased early clinical and subclinical markers of atherosclerosis seen in
PCOS (endothelial dysfunction, impaired pulse wave
velocity, increased carotid intima media wall thickness,
presence of carotid plaque and increased coronary artery
calcification) [34,57] are further exacerbated by obesity
[27,58,59]. Given that large longitudinal cohort studies
have reported up to 65% of CVD deaths occur in subjects
with impaired glucose metabolism [60] and that IGT and
DM2 are increased in PCOS, it would be expected that
women with PCOS would have increased CVD risk.
There is currently a lack of long-term studies in PCOS to
appropriately address CVD risk. Some studies support an
increased risk of CVD in PCOS [18], but these findings
are not universal [61] and further research is needed. A
recent study in postmenopausal women with premenopausal features of PCOS noted higher prevalence of
angiographic coronary artery disease and that PCOS was
associated with worsened cardiovascular event-free survival [18].
Psychological features of PCOS

Most research has focused on the biological and physiological aspects of the syndrome. The challenges to femi-

Page 5 of 10

nine identity and body image due to obesity, acne and

excess hair, as well infertility and long-term healthrelated concerns compromise quality of life and adversely
impact on mood and psychological well-being [23,62].
Limited studies to date have reported that women who
have PCOS are more prone to depression, anxiety, low
self-esteem, negative body image, and psychosexual dysfunction [63,64]. The other critical aspect of psychosocial
impact in PCOS is the negative impact of mood disturbance, poor self-esteem and reduced psychological wellbeing on motivation and on ability to implement and sustain successful lifestyle changes that are critical in this
condition [19]. These issues all need to be explored and
addressed as part of PCOS assessment and management.
Investigations and assessment in PCOS

There is no single diagnostic test for PCOS. Key investigations include prolactin and thyroid stimulating hormone to exclude other disorders and testosterone, SHBG
and free androgen index to assess androgen status [33].
Other investigations include a pelvic ultrasound for ovarian morphology and endometrial thickness. An oral glucose tolerance test (rather than fasting glucose) and lipid
profiles are appropriate in all women at diagnosis and 1 to
2 yearly after this, where women are overweight or have
an increased risk of DM2 (for example, family history of
DM2 in first-degree relatives, increased age or high-risk
ethnic group). As noted, insulin levels should not be measured in clinical practice because of assay variability and
inaccuracy. Metabolic syndrome and abnormal glucose
metabolism best reflect insulin resistance in this population.

Treatment of PCOS
Targeted approach to therapy

Treatment options need to be tailored to the clinical presentation. Education on short-term and long-term sequalae of PCOS from a reliable independent source is
important in allaying anxiety and minimising the impact
of illness in chronic disease (Table 2). As a prelude to
treatment psychological features need to be acknowledged, discussed and counselling considered [65], to
enable lifestyle change which is unlikely to be successful
without first addressing education and psychosocial
issues (Figure 2 and Appendix 2).
Weight loss, exercise and lifestyle interventions

Lifestyle change is first line treatment in an evidencebased approach in the management of the majority of
PCOS women who are overweight [19]. Furthermore,
prevention of excess weight gain should be emphasised in
all women with PCOS of both normal or increased body
weight. As little as 5% to 10% weight loss has significant
clinical benefits improving psychological outcomes [66],
reproductive features (menstrual cyclicity, ovulation and

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

Table 2: Evidence-based government funded resources to

inform consumers and/or health professionals in
polycystic ovary syndrome (PCOS)
Resource

Description

http://
www.managingpcos.org.au

Evidence-based independent
consumer and health
professional information

http://www.jeanhailes.org.au

Evidence-based independent
consumer and health
professional information

PCOS patient fact sheets

Freely available: link from

website above

fertility) [9,67] and metabolic features (insulin resistance

and risk factors for CVD and DM2). Evidence shows that
lifestyle change with small achievable goals results in clinical benefits even when women remain in the overweight
or obese range, [9,68,69]. Standard dietary management
of obesity and related comorbidities [70] is a nutritionally
adequate, low fat (approximately 30% of energy, saturated
fat approximately 10%), moderate protein (approximately
15%) and high carbohydrate intake (approximately 55%),
with increased fibre-rich wholegrain breads, cereals,
fruits and vegetables and moderate regular exercise. A
moderate energy reduction diet (500 to 1,000 kcal/day
reduction) reduces body weight by 7% to 10% over a
period of 6 to 12 months. Simple and practical tips that
can be covered in minutes in medical consultation
include targeting fruit juice, soft drinks, portion sizes and
high-fat foods. Incorporating simple moderate physical

Figure 2 Summary of a targeted approach to therapy in polycystic ovary syndrome (PCOS). Reproduced with permission from [82].

Page 6 of 10

activity including structured exercise (at least 30 min/

day) and incidental exercise increases weight loss and
improves clinical outcomes in PCOS, compared to diet
alone [71]. Exercise alone also improves clinical outcomes. As in the general population, goals for exercise
must focus on overall health benefits not weight loss per
se.
Fad diets are not encouraged as short-term weight loss,
if achieved, is rarely sustainable [72]. The advantages of
specific dietary approaches over that of caloric restriction
alone are still unclear and more research is needed. Proposed specific dietary approaches in PCOS include high
protein, low carbohydrate and low glycaemic index/glycaemic load diets. A number of small studies assessing
specific dietary approaches in PCOS show similar results
for diets moderately increased in dietary protein or carbohydrate [73-75] with one study reporting greater
weight loss where a high protein supplement was added
to a standard energy reduced diet [76]. Two small studies
have assessed very low carbohydrate diets in PCOS, and
one study reported on an audit of reduced glycaemic load
diets in clinical practice. While reductions in weight,
BMI, waist circumference, fasting insulin or testosterone
were reported, these studies lacked a control group [7779]. The current evidence suggests that a range of dietary
strategies, as long as they are safe, nutritionally adequate
and sustainable in the long term, will similarly improve
weight, and reproductive and metabolic features in PCOS
[19].
Pharmacological therapy in PCOS

There is currently no ideal medical PCOS therapy that

fully reverses underlying hormonal disturbances and
treats all clinical features. The OCP does improve hyperandrogenism and insulin sensitisers (primarily Metformin) reduce insulin resistance in PCOS [80].
Generally, medical therapy is targeted to symptoms and
should not be used as an alternative to lifestyle therapy in
PCOS (Figure 2). Simple medical therapy is summarised
in Appendix 2. The OCP has long been used in PCOS to
induce regular cycles, protect the endometrium and treat
hyperandrogenism. Mechanisms of action include a significant first pass hepatic effect, increasing production of
hepatic proteins including sex hormone binding globulin.
This reduces free circulating androgen levels, even with
low dose OCPs. This important mechanism of antiandrogenic action does not occur with progestin alone or nonoral oestrogen containing contraceptive preparations.
The OCP also reduces ovarian androgen production.
There has been concerning data that the OCP can
increase insulin resistance and worsen glucose tolerance.
Studies are inadequate and data conflicting with more
research needed, however consideration should be given
to cardiometabolic effects of medical therapy and low

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

dose OCP preparations may be a preferable alternative,

with similar efficacy and reduced cardiometabolic effects
[80].
Metformin has had an increasing role in PCOS management [22,81], improving clinical features (ovulation,
cycle regulation, and potentially hirsutism) with positive
cardiometabolic effects [22,81]. It does not appear to
induce weight loss, although based on studies in DM2 it
may assist in preventing future weight gain. Based on
International Diabetes Federation recommendations
[48,80], metformin has a role in prevention of diabetes
where lifestyle therapy is inadequate. Given the increased
insulin resistance and high risk of DM2, this includes
PCOS especially if other risk factors including excess
weight, family history of DM2, metabolic syndrome or
prediabetes exist [22]. In infertility, the role of metformin
remains controversial. It does reduce hyperstimulation in
those on other fertility therapies, however more research
here is important. When using metformin it is better tolerated if started at 500 mg of slow release daily and
increased over weeks to months to reach 2 g daily. Lactic
acidosis is a rare side effect in those with other significant
illnesses including renal impairment [22]. It is important
to note that neither metformin nor the OCP are approved
by most regulatory authorities specifically for PCOS. The
OCP is indicated for contraception and metformin for
the treatment of diabetes. However, both treatments are
recommended by international and national endocrine
societies and are evidence based [20]. A detailed discussion of infertility therapy is beyond the scope of this
review, however clomiphene is generally used as initial
medical therapy.

Conclusions
PCOS is a common complex condition in women associated with psychological, reproductive and metabolic features. It is a chronic disease with manifestations across
the lifespan and represents a major health and economic
burden. Both hyperandrogenism and insulin resistance
contribute to pathophysiology of PCOS. Insulin resistance occurs in the majority of women with PCOS, especially those who are overweight, and these women have a
high risk of metabolic syndrome, prediabetes and DM2.
Management should focus on support, education,
addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as
required. Treatment for the large majority is lifestyle
focused and an aggressive lifestyle-based multidisciplinary approach is optimal in most cases to manage the
features of PCOS and prevent long-term complications.
Small achievable goals of 5% loss of body weight result in
significant clinical improvement even if women remain
clinically in the unhealthy overweight or obese range.
Addressing hyperandrogenism is clinically important and

Page 7 of 10

monitoring for and managing longer-term metabolic

complications, including dyslipidaemia, IGT, DM2, and
cardiovascular risk factors, is crucial. Consideration
should be given to screening high-risk family members
for metabolic abnormalities also. Overall, further
research is needed in this complex condition. In the
interim, comprehensive evidence-based guidelines are
needed to guide consumers and clinicians in optimal
PCOS management.

Appendix 1
Reproductive, metabolic and psychosocial features of
polycystic ovary syndrome (PCOS)
Clinical features of PCOS

(1) Reproductive features: hyperandrogenism, hirsutism,

ovulatory and menstrual dysfunction, infertility, complications in pregnancy, miscarriage, pregnancy-induced
diabetes (gestational diabetes), pregnancy-induced
hypertensive disorders and neonatal complications and
increased endometrial hyperplasia.
(2) Metabolic features: insulin resistance, metabolic
syndrome, dyslipidaemia, high rates of premature
impaired glucose tolerance, type 2 diabetes and increased
cardiovascular risk factors.
(3) Psychological features: anxiety, depression, poor
self-esteem, reduced quality of life, negative body image.

Appendix 2
Summary of treatment options in polycystic ovary
syndrome (PCOS)
Oligomenorrhoea/amenorrhoea

Lifestyle change (5% to 10% weight loss and structured exercise).

Oral contraceptive pill (OCP; low oestrogen doses,
for example 20 g may be preferable).
Cyclic progestins (for example, 10 mg medroxyprogesterone acetate for 14 days every 2 to 3 months).
Metformin (improves ovulation and menstrual
cyclicity).
Hirsutism treatment recommendations

Cosmetic therapy.
Laser treatment.
Eflornithine cream can be added and may induce a
more rapid response.
Pharmacological therapy

Medical therapy if patient concerned about hirsutism and cosmetic therapy ineffective, inaccessible or
unaffordable.
Primary therapy is the OCP (monitor glucose tolerance in those at risk of diabetes).
Antiandrogen monotherapy should not be used
without adequate contraception.
Trial therapies for 6 months before changing dose
or medication.

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

Combination therapy: if 6 months of OCP is ineffective, add antiandrogen to OCP (daily spironolactone 50 mg twice a day or cyproterone acetate 25 mg/
day for days 1 to 10 of the active OCP tablets).

Page 8 of 10

3.

4.

Infertility

Obesity independently exacerbates infertility and

reduces effectiveness of interventions. Maternal and
foetal pregnancy risks are greater and long-term metabolic outcomes in the child are related to maternal
weight at conception. Consistent with international
guidelines, women who are overweight prior to conception should be advised on folate, smoking cessation, weight loss and optimal exercise, prior to
additional interventions.
Given age-related infertility, advise women to optimise family planning.
Infertility therapies may include clomiphene, gonadotrophins and in vitro fertilisation.
Metabolic syndrome, prediabetes, diabetes and
cardiovascular disease risk

Obesity independently causes metabolic complications;

lifestyle/exercise is critical:
Lifestyle change with a 5% weight loss reduces diabetes risk by approximately 50% to 60% in high-risk
groups [49].
Metformin* reduces the risk of diabetes by approximately 50% in high-risk groups [49].
*Metformin and the OCP are not currently approved
for use to manage PCOS by many regulatory bodies. The
OCP is primarily indicated for contraception and metformin for diabetes. However, their use is recommended
by international and national specialist societies and is
evidence based [22].

5.

6.

7.

8.

9.

10.
11.

12.

13.

14.
15.

16.

17.

Competing interests
The authors declare that they have no competing interests.
Authors' contributions
HT, AD and LM all made substantial contributions to conception and design of
the paper, were involved in drafting the manuscript and revising it critically for
important intellectual content and have given final approval of the version to
be published.
Author Details
1Jean Hailes Clinical Research Unit, School of Public Health and Preventive
Medicine, Monash University, Clayton, Australia and 2Diabetes Unit, Southern
Health, Clayton, Australia
Received: 13 January 2010 Accepted: 30 June 2010
Published: 30 June 2010

This
BMC
2010
is
article
Medicine
an
Teede
Open
is available
2010,
etAccess
al; licensee
8:41
from:
articleBioMed
http://www.biomedcentral.com/1741-7015/8/41
distributed
Central
under
Ltd.the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

References
1. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC,
Spina GG, Zapanti ED, Bartzis MI: A survey of the polycystic ovary
syndrome in the Greek island of Lesbos: hormonal and metabolic
profile. J Clin Endocrinol Metab 1999, 84:4006-4011.
2. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R:
Prevalence of the polycystic ovary syndrome in unselected black and
white women of the southeastern United States: a prospective study. J
Clin Endocrinol Metab 1998, 83:3078-3082.

18.

19.

20.

21.

Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale

HF: A prospective study of the prevalence of the polycystic ovary
syndrome in unselected Caucasian women from Spain. J Clin
Endocrinol Metab 2000, 85:2434-2438.
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO: The
prevalence and features of the polycystic ovary syndrome in an
unselected population. J Clin Endocrinol Metab 2004, 89:2745-2749.
March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ: The
prevalence of polycystic ovary syndrome in a community sample
assessed under contrasting diagnostic criteria. Hum Reprod 2010,
25:544-551.
Alvarez-Blasco F, Botella-Carretero JI, San Millan JL, Escobar-Morreale HF:
Prevalence and characteristics of the polycystic ovary syndrome in
overweight and obese women. Arch Intern Med 2006, 166:2081-2086.
Azziz R, Sanchez LA, Knochenhauer ES, Moran C, Lazenby J, Stephens KC,
Taylor K, Boots LR: Androgen excess in women: experience with over
1000 consecutive patients. J Clin Endocrinol Metab 2004, 89:453-462.
Azziz R, Marin C, Hoq L, Badamgarav E, Song P: Health care-related
economic burden of the polycystic ovary syndrome during the
reproductive life span. J Clin Endocrinol Metab 2005, 90:4650-4658.
Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ: Weight loss in
obese infertile women results in improvement in reproductive
outcome for all forms of fertility treatment. Hum Reprod 1998,
13:1502-1505.
Legro RS, Strauss JF: Molecular progress in infertility: polycystic ovary
syndrome. Fertil Steril 2002, 78:569-576.
Doi SA, Al-Zaid M, Towers PA, Scott CJ, Al-Shoumer KA: Ovarian steroids
modulate neuroendocrine dysfunction in polycystic ovary syndrome.
J Endocrinol Invest 2005, 28:882-892.
Legro RS, Castracane VD, Kauffman RP: Detecting insulin resistance in
polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv
2004, 59:141-154.
Vrbikova J, Cibula D, Dvorakova K, Stanicka S, Sindelka G, Hill M, Fanta M,
Vondra K, Skrha J: Insulin sensitivity in women with polycystic ovary
syndrome. J Clin Endocrinol Metab 2004, 89:2942-2945.
Moran L, Teede H: Metabolic features of the reproductive phenotypes
of polycystic ovary syndrome. Hum Reprod Update 2009, 15:477-488.
Diamanti-Kandarakis E, Papavassiliou AG: Molecular mechanisms of
insulin resistance in polycystic ovary syndrome. Trends Mol Med 2006,
12:324-332.
Balen AH, Conway GS, Kaltsas G, Techatrasak K, Manning PJ, West C, Jacobs
HS: Polycystic ovary syndrome: the spectrum of the disorder in 1741
patients. Hum Reprod 1995, 10:2107-2111.
Kiddy DS, Sharp PS, White DM, Scanlon MF, Mason HD, Bray CS, Polson
DW, Reed MJ, Franks S: Differences in clinical and endocrine features
between obese and non-obese subjects with polycystic ovary
syndrome: an analysis of 263 consecutive cases. Clin Endocrinol (Oxf )
1990, 32:213-220.
Shaw LJ, Bairey Merz CN, Azziz R, Stanczyk FZ, Sopko G, Braunstein GD,
Kelsey SF, Kip KE, Cooper-Dehoff RM, Johnson BD, Vaccarino V, Reis SE,
Bittner V, Hodgson TK, Rogers W, Pepine CJ: Postmenopausal women
with a history of irregular menses and elevated androgen
measurements at high risk for worsening cardiovascular event-free
survival: results from the National Institutes of Health-National Heart,
Lung, and Blood Institute sponsored Women's Ischemia Syndrome
Evaluation. J Clin Endocrinol Metab 2008, 93:1276-1284.
Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ: Treatment of
obesity in polycystic ovary syndrome: a position statement of the
Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril
2009, 92:1966-1982.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group:
Revised 2003 consensus on diagnostic criteria and long-term health
risks related to polycystic ovary syndrome Society. Fertil Steril 2004,
81:19-25.
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale
HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF,
Androgen Excess Society: Position statement: criteria for defining
polycystic ovary syndrome as a predominantly hyperandrogenic
syndrome: an Androgen Excess Society guideline. J Clin Endocrinol
Metab 2006, 91:4237-4245.

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

22. Teede H, Hutchison SK, Zoungas S: The management of insulin

resistance in polycystic ovary syndrome. Trends Endocrinol Metab 2007,
18:273-279.
23. Deeks AA, Gibson-Helm ME, Teede HJ: Anxiety and depression in
polycystic ovary syndrome: a comprehensive investigation. Fertil Steril
2010, 93:2421-2423.
24. Himelein MJ, Thatcher SS: Polycystic ovary syndrome and mental
health: A review. Obst Gynecol Surv 2006, 61:723-732.
25. Boomsma CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon
NS: A meta-analysis of pregnancy outcomes in women with polycystic
ovary syndrome. Hum Reprod Update 2006, 12:673-683.
26. Apridonidze T, Essah PA, Iuorno MJ, Nestler JE: Prevalence and
characteristics of the metabolic syndrome in women with polycystic
ovary syndrome. J Clin Endocrinol Metab 2005, 90:1929-1935.
27. Legro RS, Kunselman AR, Dodson WC, Dunaif A: Prevalence and
predictors of risk for type 2 diabetes mellitus and impaired glucose
tolerance in polycystic ovary syndrome: a prospective, controlled
study in 254 affected women. J Clin Endocrinol Metab 1999, 84:165-169.
28. Coviello AD, Legro RS, Dunaif A: Adolescent girls with polycystic ovary
syndrome have an increased risk of the metabolic syndrome
associated with increasing androgen levels independent of obesity
and insulin resistance. J Clin Endocrinol Metab 2006, 91:492-497.
29. Palmert MR, Gordon CM, Kartashov AI, Legro RS, Emans SJ, Dunaif A:
Screening for abnormal glucose tolerance in adolescents with
polycystic ovary syndrome. J Clin Endocrinol Metab 2002, 87:1017-1023.
30. Brassard M, AinMelk Y, Baillargeon JP: Basic infertility including
polycystic ovary syndrome. Med Clin North Am 2008, 92:1163-1192. xi
31. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale
HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF,
Task Force on the Phenotype of the Polycystic Ovary Syndrome of The
Androgen Excess and PCOS Society: The Androgen Excess and PCOS
Society criteria for the polycystic ovary syndrome: the complete task
force report. Fertil Steril 2009, 91:456-488.
32. Cedergren MI: Optimal gestational weight gain for body mass index
categories. Obstet Gynecol 2007, 110:759-764.
33. Norman RJ, Dewailly D, Legro RS, Hickey TE: Polycystic ovary syndrome.
Lancet 2007, 370:685-697.
34. Meyer C, McGrath BP, Teede HJ: Overweight women with polycystic
ovary syndrome have evidence of subclinical cardiovascular disease. J
Clin Endocrinol Metab 2005, 90:5711-5716.
35. Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB: Lipoprotein lipid
concentrations and cardiovascular risk in women with polycystic ovary
syndrome. J Clin Endocrinol Metab 1985, 61:946-951.
36. Wild RA: Obesity, lipids, cardiovascular risk, and androgen excess. Am J
Med 1995, 98:27S-32S.
37. Talbott E, Clerici A, Berga SL, Kuller L, Guzick D, Detre K, Daniels T, Engberg
RA: Adverse lipid and coronary heart disease risk profiles in young
women with polycystic ovary syndrome: results of a case-control
study. J Clin Epidemiol 1998, 51:415-422.
38. Wild RA, Bartholomew MJ: The influence of body weight on lipoprotein
lipids in patients with polycystic ovary syndrome. Am J Obstet Gynecol
1988, 159:423-427.
39. Dunaif A, Finegood DT: Beta-cell dysfunction independent of obesity
and glucose intolerance in the polycystic ovary syndrome. J Clin
Endocrinol Metab 1996, 81:942-947.
40. O'Meara N, Blackman JD, Ehrmann DA, Barnes RB, Jaspan JB, Rosenfield RL,
Polonsky KS: Defects in beta-cell function in functional ovarian
hyperandrogenism. J Clin Endocrinol Metab 1993, 76:1241-1247.
41. Dunaif A, Segal KR, Futterweit W, Dobrjansky A: Profound peripheral
insulin resistance, independent of obesity, in polycystic ovary
syndrome. Diabetes 1989, 38:1165-1174.
42. Dunaif A: Insulin resistance and the polycystic ovary syndrome:
mechanism and implications for pathogenesis. Endocr Rev 1997,
18:774-800.
43. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J:
Prevalence of impaired glucose tolerance and diabetes in women with
polycystic ovary syndrome. Diabetes Care 1999, 22:141-146.
44. Barr ELM, Magliano DJ, Zimmet PZ, Polkinghorne KR, Atkins RC, Dunstan
DW, Murray SG, Shaw JE: AusDiab 2005: The Australian Diabetes,
Obesity and Lifestyle Study. Melbourne, Australia: International
Diabetes Institute; 2006.

Page 9 of 10

45. Norman RJ, Masters L, Milner CR, Wang JX, Davies MJ: Relative risk of
conversion from normoglycaemia to impaired glucose tolerance or
non-insulin dependent diabetes mellitus in polycystic ovarian
syndrome. Hum Reprod 2001, 16:1995-1998.
46. Legro RS, Gnatuk CL, Kunselman AR, Dunaif A: Changes in glucose
tolerance over time in women with polycystic ovary syndrome: a
controlled study. J Clin Endocrinol Metab 2005, 90:3236-3242.
47. Boudreaux MY, Talbott EO, Kip KE, Brooks MM, Witchel SF: Risk of T2DM
and impaired fasting glucose among PCOS subjects: results of an 8year follow-up. Curr Diab Rep 2006, 6:77-83.
48. Alberti KG, Zimmet P, Shaw J: International Diabetes Federation: a
consensus on Type 2 Diabetes prevention. Diabet Med 2007,
24:451-463.
49. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker
EA, Nathan DM: Reduction in the incidence of type 2 diabetes with
lifestyle intervention or metformin. N Engl J Med 2002, 346:393-403.
50. Dunstan D, Zimmet P, Welborne T, Sicree RTA, Atkins R, Cameron A, Shaw
J, Chadaban S: Diabetes and associated disorders in Australia 2000 - the
accelerating epidemic. In Australian Diabetes, Obesity and Lifestyle Report
Melbourne, Australia: The International Diabetes Institute; 2001.
51. Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE:
Glucose intolerance in polycystic ovary syndrome - a position
statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007,
92:4546-4556.
52. Sam S, Legro RS, Essah PA, Apridonidze T, Dunaif A: Evidence for
metabolic and reproductive phenotypes in mothers of women with
polycystic ovary syndrome. Proc Natl Acad Sci USA 2006, 103:7030-7035.
53. Crisosto N, Codner E, Maliqueo M, Echiburu B, Sanchez F, Cassorla F, SirPetermann T: Anti-Mullerian hormone levels in peripubertal daughters
of women with polycystic ovary syndrome. J Clin Endocrinol Metab
2007, 92:2739-2743.
54. Baillargeon J, Carpentier AC: Brothers of women with polycystic ovary
syndrome are characterised by impaired glucose tolerance, reduced
insulin sensitivity and related metabolic defects. Diabetologia 2007,
50:2424-2432.
55. Unluhizarci K, Ozocak M, Tanriverdi F, Atmaca H, Kelestimur F:
Investigation of hypothalamo-pituitary-gonadal axis and glucose
intolerance among the first-degree female relatives of women with
polycystic ovary syndrome. Fertil Steril 2007, 87:1377-1382.
56. Yilmaz M, Bukan N, Ersoy R, Karakoc A, Yetkin I, Ayvaz G, Cakir N, Arslan M:
Glucose intolerance, insulin resistance and cardiovascular risk factors
in first degree relatives of women with polycystic ovary syndrome.
Hum Reprod 2005, 20:2414-2420.
57. Meyer C, McGrath BP, Cameron J, Kotsopoulos D, Teede HJ: Vascular
dysfunction and metabolic parameters in polycystic ovary syndrome.
J Clin Endocrinol Metab 2005, 90:4630-4635.
58. Legro RS, Kunselman AR, Dunaif A: Prevalence and predictors of
dyslipidemia in women with polycystic ovary syndrome. Am J Med
2001, 111:607-613.
59. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN, Group
PCTS: Prevalence and predictors of the metabolic syndrome in women
with polycystic ovary syndrome. J Clin Endocrinol Metab 2006, 91:48-53.
60. Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW,
Cameron AJ, Dwyer T, Taylor HR, Tonkin AM, Wong TY, McNeil J, Shaw JE:
Risk of cardiovascular and all-cause mortality in individuals with
diabetes mellitus, impaired fasting glucose, and impaired glucose
tolerance: the Australian Diabetes, Obesity, and Lifestyle Study
(AusDiab). Circulation 2007, 116:151-157.
61. Pierpoint T, McKeigue PM, Isaacs AJ, Wild SH, Jacobs HS: Mortality of
women with polycystic ovary syndrome at long-term follow-up. J Clin
Epidemiol 1998, 51:581-586.
62. Coffey S, Bano G, Mason HD: Health-related quality of life in women
with polycystic ovary syndrome: a comparison with the general
population using the Polycystic Ovary Syndrome Questionnaire
(PCOSQ) and the Short Form-36 (SF-36). Gynecol Endocrinol 2006,
22:80-86.
63. Coffey S, Mason H: The effect of polycystic ovary syndrome on healthrelated quality of life. Gynecol Endocrinol 2003, 17:379-386.
64. Deeks A, Gibson-Helm M, Teede H: Anxiety and depression in polycystic
ovary syndrome (PCOS): a comprehensive investigation. Fertil Steril
2010, 93:2421-2423.

Teede et al. BMC Medicine 2010, 8:41

http://www.biomedcentral.com/1741-7015/8/41

65. Chen TH, Lu RB, Chang AJ, Chu DM, Chou KR: The evaluation of
cognitive-behavioral group therapy on patient depression and selfesteem. Arch Psychiatr Nurs 2006, 20:3-11.
66. Galletly C, Clark A, Tomlinson L, Blaney F: A group program for obese,
infertile women: weight loss and improved psychological health. J
Psychosom Obstet Gynaecol 1996, 17:125-128.
67. Huber-Buchholz MM, Carey DG, Norman RJ: Restoration of reproductive
potential by lifestyle modification in obese polycystic ovary syndrome:
role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol
Metab 1999, 84:1470-1474.
68. Hamilton-Fairley D, Kiddy D, Anyaoku V, Koistinen R, Seppala M, Franks S:
Response of sex hormone binding globulin and insulin-like growth
factor binding protein-1 to an oral glucose tolerance test in obese
women with polycystic ovary syndrome before and after calorie
restriction. Clin Endocrinol (Oxf ) 1993, 39:363-367.
69. Wahrenberg H, Ek I, Reynisdottir S, Carlstrom K, Bergqvist A, Arner P:
Divergent effects of weight reduction and oral anticonception
treatment on adrenergic lipolysis regulation in obese women with the
polycystic ovary syndrome. J Clin Endocrinol Metab 1999, 84:2182-2187.
70. Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ: Comparison
of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss
and heart disease risk reduction: a randomized trial. JAMA 2005,
293:43-53.
71. Poehlman ET, Dvorak RV, DeNino WF, Brochu M, Ades PA: Effects of
resistance training and endurance training on insulin sensitivity in
nonobese, young women: a controlled randomized trial. J Clin
Endocrinol Metab 2000, 85:2463-2468.
72. NHaMRC: Clinical Practice Guidelines for the Management of
Overweight and Obesity in Adults. Canberra, Australia: Australian
Government Publishing Service; 2003.
73. Moran LJ, Noakes M, Clifton PM, Tomlinson L, Galletly C, Norman RJ:
Dietary composition in restoring reproductive and metabolic
physiology in overweight women with polycystic ovary syndrome. J
Clin Endocrinol Metab 2003, 88:812-819.
74. Stamets K, Taylor DS, Kunselman A, Demers LM, Pelkman CL, Legro RS: A
randomized trial of the effects of two types of short-term hypocaloric
diets on weight loss in women with polycystic ovary syndrome. Fertil
Steril 2004, 81:630-637.
75. Moran LJ, Noakes M, Clifton PM, Wittert GA, Williams G, Norman RJ: Shortterm meal replacements followed by dietary macronutrient restriction
enhance weight loss in polycystic ovary syndrome. Am J Clin Nutr 2006,
84:77-87.
76. Kasim-Karakas SE, Almario RU, Cunningham W: Effects of protein versus
simple sugar intake on weight loss in polycystic ovary syndrome
(according to the National Institutes of Health criteria). Fertil Steril 2009,
92:262-270.
77. Hays JH, DiSabatino A, Gorman RT, Vincent S, Stillabower ME: Effect of a
high saturated fat and no-starch diet on serum lipid subfractions in
patients with documented atherosclerotic cardiovascular disease.
Mayo Clin Proc 2003, 78:1331-1336.
78. Mavropoulos JC, Yancy WS, Hepburn J, Westman EC: The effects of a lowcarbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot
study. Nutr Metab 2006, 2:35.
79. Herriot AM, Whitcroft S, Jeanes Y: An retrospective audit of patients with
polycystic ovary syndrome: the effects of a reduced glycaemic load
diet. J Hum Nutr Diet 2008, 21:337-345.
80. Meyer C, McGrath BP, Teede HJ: Effects of medical therapy on insulin
resistance and the cardiovascular system in polycystic ovary
syndrome. Diabetes Care 2007, 30:471-478.
81. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH: Insulin-sensitising drugs
(metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women
with polycystic ovary syndrome, oligo amenorrhoea and subfertility.
Cochrane Database Syst Rev 2009, 4:CD003053.
82. Teede H, Zoungas S, Deeks A, Farrell E, Moran L, Vollenhoven B: Check:
independent learning program for GPs. Polycystic ovary syndrome.
Volume Unit 432. Edited by: Royal Australian College of General
Practitioners. South Melbourne, Victoria: Royal Australian College of
General Practitioners; 2008.
83. Zawadzki J, Dunaif A: Diagnostic criteria for polycystic ovary syndrome:
towards a rational approach. In Polycystic Ovary Syndrome Current Issues
in Endocrinology and Metabolism Edited by: Dunaif A, Givens J, Haseltine F,
Marrian G. Boston, MA: Blackwell Scientific; 1992:377-384.

Page 10 of 10

Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1741-7015/8/41/prepub
doi: 10.1186/1741-7015-8-41
Cite this article as: Teede et al., Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that
impacts on health across the lifespan BMC Medicine 2010, 8:41